The overall goals of this project are: (1) to continue our longstanding studies of the biological aspects of murine lymphomagenesis induced by radiation and related viruses. Specifically, we wish to define the cell population(s) in the bone marrow of irradiated mice which contains the novel transmissible lymphomagen, as a first step in its identification, and also as an important step in reconciling normal and neoplastic hematolymphoid cell differentiation lineages. Similar techniques of cell separation based on immunomagnetic bead separation technology, followed by flow cytometry will be used to identify normal bone marrow cells which prevent radiation lymphomagenesis; and also target cells for neoplastic transformation. The role of stromal cells in the progression of preleukemic cells will be analyzed. The studies in the murine model will be extended to a direct examination of the effects of radiation and of human lymphotropic viruses (HTLV-I and HTLV-II) on human organ systems in vivo, by making use of our recently described hematochimeric SCID-hu mice. The parameters which we have worked out in murine radiation lymphomagenesis will be tested in the SCID-hu system. With respect to the human retroviruses, evidence of infection will be sought following their inoculation in SCID-hu mice and, if detected, the course of disease pathogenesis will be evaluated. Because of its potential value to the study of human disease, major emphasis will be placed on this aspect of the project.